Neuroprotection of geniposide against hydrogen peroxide induced PC12 cells injury: involvement of PI3 kinase signal pathway
Neuroprotection of geniposide against hydrogen peroxide induced PC12 cells injury: involvement of PI3 kinase signal pathway
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京尼平苷对过氧化氢诱导的 PC12 细胞损伤的神经保护作用：PI3 激酶信号通路的参与
DOI：
10.1038/aps.2008.25
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发表时间：
2009-02-01
影响因子：
8.2
通讯作者：
Hu, Yin-he
中科院分区：
文献类型：
--
作者：
Liu, Jian-hui;Yin, Fei;Hu, Yin-he
目的：氧化应激在阿尔茨海默病中导致神经元变性的致病级联反应中起关键作用。因此，通过抗氧化剂诱导内源性抗氧化蛋白似乎是延缓疾病进展的一种非常合理的策略。在之前的工作中，我们发现了京尼平苷的神经营养和神经保护作用，这是由于激活胰高血糖素样肽1受体（GLP-1R）。本研究探讨PI3激酶信号通路在京尼平苷对PC12细胞的神经保护作用中的作用。方法：采用MTT法测定细胞活力。Hoechst和PI双染色检测细胞凋亡。Western blot检测Bcl-2蛋白表达及Akt308、Akt473、GSK-3β、PDK1磷酸化水平。结果：京尼平苷可诱导抗凋亡蛋白Bcl-2的表达，抑制h2o2诱导的PC12细胞凋亡，并可通过PI3K选择性抑制剂LY294002预孵育抑制该作用。此外，京尼平苷在氧化应激条件下增强了Akt308、Akt473、GSK-3β和PDK1的磷酸化。结论：上述结果表明PI3K信号通路参与了京尼平苷对PC12细胞h2o2氧化损伤的神经保护作用。
Aim:Oxidative stress plays a critical role in the pathogenic cascade leading to neuronal degeneration in AD. Consequently, the induction of endogenous antioxidative proteins by antioxidants seems to be a very reasonable strategy for delaying the disease's progression. In previous work, we identified the neurotrophic and neuroprotective effects of geniposide, which result from the activation of glucagon-like peptide 1 receptor (GLP-1R). In this study, we explore the role of PI3 kinase signaling pathway in the neuroprotection of geniposide in PC12 cells.Methods:Cell viability was determined by MTT assay. Apoptosis was detected by Hoechst and PI double staining. The protein expression of Bcl-2 and phosphorylation of Akt308, Akt473, GSK-3β, and PDK1 was measured by Western blot.Results:Geniposide induced the expression of the antiapoptotic protein Bcl-2, which inhibited apoptosis in PC12 cells induced by H 2 O 2, and this effect could be inhibited by preincubation with LY294002, a selective inhibitor of PI3K. Furthermore, geniposide enhanced the phosphorylation of Akt308, Akt473, GSK-3β and PDK1 under conditions of oxidative stress.Conclusion:These results demonstrate that the PI3K signaling pathway is involved in the neuroprotection of geniposide in PC12 cells against the oxidative damage induced by H 2 O 2 in PC12 cells.